Necrotizing enterocolitis intestinal barrier function protection by antenatal dexamethasone and surfactant-D in a rat model

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common gastrointestinal disorder in premature neonates. Possible therapeutic approaches are centered on promoting maturation of the gastrointestinal mucosal barrier. Studies have demonstrated that antenatal administration of corticosteroids can decrease NEC incidence and mortality. METHODS: Pregnant rat dams were administered dexamethasone 48 h prior to delivery. The pups were subjected to an experimental NEC-like injury protocol. Ileal tissues and sera were collected and evaluated for inflammatory cytokines, gut permeability and expressions and localizations of tight junction proteins, and surfactant protein-D by immunohistochemistry/immunofluorescent staining. Intestinal epithelial cells (IEC-6) were pretreated with SP-D to examine the effect of SP-D on tight junction protein expressions when challenged with platelet-activating factor and lipopolysaccharide to model proinflammatory insults. RESULTS: Antenatal dexamethasone reduced systemic inflammation, preserved intestinal barrier integrity, and stimulated SP-D expression on the intestinal mucosal surface in pups exposed to NEC-like injury. Pretreatment of SP-D blocked platelet-activating factor/lipopolysaccharide-induced tight junction disruption in IEC-6 cells in vitro. CONCLUSIONS: Antenatal dexamethasone preserves the development of intestinal mucosal barrier integrity and reduces incidence and morbidity from an experimental NEC-like injury model. Dexamethasone upregulation of intestinal SP-D-protective effects on tight junction proteins. IMPACT: Antenatal administration of dexamethasone can function in concert with intestinal surfactant protein-D to decrease systemic inflammatory responses, and protect intestinal barrier integrity in a neonatal rat model of NEC. A novel role of intestinal SP-D in preserving tight junction protein structures under inflammatory conditions. We describe the intestinal SP-D—an overlooked role of antenatal dexamethasone in neonatal NEC?